Glycyrrhizic Acid Prevents Diabetic Nephropathy By Activating AMPK/SIRT1/PGC-1? Signaling

Objective To investigate the protective effect of glycyrrhizic acid on diabetic nephropathy and whether glycyrrhizic acid can protect diabetic nephropathy via AMPK/ SIRT1 / PGC-1? signaling pathway in diabetic db/db mice.Methods The model of diabetic nephropathy was prepared by using male db/db mice,and glycyrrhizic acid intervention was used.The mice were divided into db group(db /db mice),db+g group(db/db mice+glycyrrhizic acid intervention group),m group(db/m mice),m+g group(db/m mice+ glycyrrhizic acid intervention group)and n group(normal C57BL/6 mice).The mice in db+g group and m+g group were injected intraperitoneally with glycyrrhizic acid(15mg/kg/d)for 8 weeks.The mice in db group,m group and n group were injected intraperitoneally with the same amount of saline.The changes of blood glucose,body weight,blood urea nitrogen and proteinuria/creatinine ratio were measured at 2,4,6,8 weeks.The content of total cholesterol and triglyceride were measured at 8 week.The changes of daily food intake were measured daily.We evaluated models with using hematoxylin-eosin(HE)staining,PAS staining,Masson staining and transmission electron microscopy(TEM);Apoptosis was determined via TUNEL staining and flow cytometry;The change of ROS was test by DHE;The contents of SOD and MDA in kidneys of mice were detected by kits.The expressions of ?-SMA,TGF-?1,p-AMPK?,SIRT1 and PGC-1? were detected by immunohistochemistry and Western blot.The expression of p-AMPK?,SIRT1 and PGC-1? mRNA was detected by the RT-PCR.Results1.Glycyrrhizic acid has no effect on the blood sugar,body weight,daily food intake,total cholesterol and triglyceride in db/ db mice,and can reduce the blood urea nitrogen and Alb/crea ratio.2.Glycyrrhizic acid can reduce cell apoptosis in db/db mouse kidney.3.Glycyrrhizic acid can reduce the content of ROS and MDA and increase the content of SOD in the kidney of db/db mice.4.Glycyrrhizic acid can reduce the expression of ?-SMA and TGF-?1 in the kidneys of db/db mice and prevent renal fibrosis.5.Glycyrrhizic acid can increase the expression of p-AMPK?,SIRT1 and PGC-1 in the kidney of db / db mice and activate the AMPK/ SIRT1/PGC-1? signaling pathway.Conclusion Glycyrrhizic acid prevents diabetic nephropathy by inhibitting apoptosis,reducing ROS production,ameliorating kidney fibrosis and activating AMPK/SIRT1/PGC-1? signaling in db/db mice.